Kinase inhibitors and method of treating cancer

Abstract

The invention is directed to a compound represented by the following structural formula and pharmaceutically acceptable salts thereof: Compounds represented by this structural formula are kinase inhibitors and are therefore disclosed herein for the treatment of cancer. Definitions for the variables in the structural formula are provided herein.

1. A compound represented by the following structural formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein:
 R a  is —F, methoxy, methyl or ethyl; 
 R 4  is —H, methyl, ethyl, 2-methoxyethyl or —CH 2 CONH 2 ; and 
 R 6  is —C═C-(optionally substituted phenyl). 
 
       
     
     
       2. The compound of  claim 1 , wherein the compound is represented by the following structural formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       3. The compound of  claim 1  wherein:
 the phenyl in —CH═CH-(phenyl) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C 1-6  alkyl, C 1-6  haloalkyl, (C 1-6  aminoalkyl), (C 1-6  alkylamino)C 1-6  alkyl, (C 1-6  dialkylamino)C 1-6  alkyl, (phenyl)C 1-6  alkyl, amino, C 1-6  alkylamino, C 1-6  dialkylamino, —(CH 2 ) 0-3 —N-piperidinyl, —(CH 2 ) 0-3 —N-morpholinyl, —(CH 2 ) 0-3 —N-pyrrolidinyl, —(CH 2 ) 0-3 —N-piperazinyl and —(CH 2 ) 0-3 —N-oxazepanyl, wherein the N-piperazinyl is optionally N′-substituted with C 1-6  alkyl or C 1-6  acyl; and 
 R 4  is —H or methyl. 
 
     
     
       4. A compound represented by the following structural formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       5. A compound of represented by the following structural formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       6. A compound represented by the following structural formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, and a compound of  claim 1  or a pharmaceutically acceptable salt thereof. 
     
     
       8. The pharmaceutical composition of  claim 7 , further comprising a therapeutic agent. 
     
     
       9. The pharmaceutical composition of  claim 8 , wherein the therapeutic agent is an anti-cancer drug. 
     
     
       10. The compound of  claim 2  wherein:
 the phenyl in —CH═CH-(phenyl) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C 1-6 alkyl, C 1-6  haloalkyl, (C 1-6  aminoalkyl), (C 1-6  alkylamino) C 1-6  alkyl, (C 1-6  dialkylamino)C 1-6  alkyl, (phenyl)C 1-6  alkyl, amino, C 1-6  alkylamino, C 1-6  dialkylamino, —(CH 2 ) 0-3 —N-piperidinyl, —(CH 2 ) 0-3 —N-morpholinyl, —(CH 2 ) 0-3 —N-pyrrolidinyl, —(CH 2 ) 0-3 —N-piperazinyl and —(CH 2 ) 0-3 —N-oxazepanyl, wherein the N-piperazinyl is optionally N′-substituted with C 1-6  alkyl or C 1-6  acyl; and 
 R 4  is —H or methyl.